Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

AIM: To investigate the decentration of the treatment zone(TZ)and the early impact on corneal higher-order aberrations(HOAs)induced by orthokeratology(OK)lenses fitted with digital corneal topography.METHODS: A retrospective longitudinal clinical study was conducted on 28 patients(28 right eyes)who were digitally fitted with OK lenses at the Laser Vision Center of Xi'an No.1 Hospital since 2023. Longitudinal measurements were taken at baseline, 1 wk, 1 and 3 mo post-treatment to assess changes in TZ diameter, decentration magnitude and direction. Furthermore, changes in corneal HOAs were observed, and correlations of decentration with each HOAs were also analyzed.RESULTS: The mean age of patients was 10.29±2.00 years, with 15 males and 13 females, and the average baseline spherical equivalent was -2.92±0.94 D. The average TZ diameters at 1 wk, 1, and 3 mo were 3.64±0.58, 3.83±0.57, and 3.69±0.55 mm, respectively, with no statistically significant differences between 1 wk and 3 mo. Horizontal decentration values were -0.43±0.28, -0.38±0.33, and -0.31±0.37 mm after wearing lenses for 1 wk, 1 and 3 mo, respectively, while vertical decentration values were -0.33±0.20, -0.33±0.23, and -0.36±0.23 mm across the same time points. The TZ consistently decentered inferotemporally, and changes in both horizontal and vertical decentration over time were not statistically significant(Fhorizontal=1.416, Phorizontal=0.252; Fvertical=0.126, Pvertical=0.882). Significant increases in total corneal HOAs, coma, and spherical aberration were observed at 5 mm optical zone post-wear(F=45.695, 33.401, and 45.091, all P<0.001). Vertical decentration at 1 wk and 1 mo was negatively correlated with total HOAs and coma(all P<0.05), while horizontal decentration at 3 mo showed a weak negative correlation with spherical aberration(P=0.037).CONCLUSION: Digitally-fitted OK lenses achieved stable TZ diameter by 1 wk post-wear, with minor inferotemporal decentration. Early post-wear corneal total HOAs, coma and sphercal aberration increased significantly, and vertical downward decentration was associated with elevated total HOAs and coma. However, correlations between decentration and HOAs weakened by 3 mo.

Abstract On September 26, 2024, a municipal hospital in Jiaxing City reported a maternal case of Listeria monocytogenes infection. In order to clarify the source of infection, the Jiaxing Center for Disease Control and Prevention immediately conducted the epidemiological investigation, laboratory testing and related disposal work. The case presented with fever (37.9 ℃), gradually intensifying paroxysmal abdominal pain without obvious cause, and went to hospital on the day of onset. Due to fetal intrauterine distress, a male infant was delivered by cesarean section on the same day. The epidemiological investigation identified that the case usually consumed fruits, often store fruits such as watermelon and grapes in the refrigerator alongside raw meat, and the refrigerator had never been cleaned or disinfected, posing a risk of cross contamination. Laboratory tests on amniotic fluid sample from the pregnant woman, infant blood sample showed positive results for Listeria monocytogenes infection. One strain of Listeria monocytogenes was detected in a smear sample from the inner wall of the refrigerator, and all the strains were ST2 type. Consuming fruits contaminated with Listeria monocytogenes may be the main source of infection. Food safety education for pregnant women and their family members should be strengthened to reduce the risk of infection.

OBJECTIVE: To explore the mechanism of BNIP3-mediated mitophagy in m.3635G>A related Leber's hereditary optic neuropathy (LHON). METHODS: A trans-mitochondrial cybrid cell line derived from a Chinese LHON patient carrying the m.3635G>A, diagnosed at the Eye Hospital of Wenzhou Medical University in September 2013, was selected as the study subject. A trans-mitochondrial cybrid cell line from a healthy control with an identical mitochondrial background was included as a control. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and Western blotting were employed to assess the expression of autophagy-related proteins, aiming to explore the role of BNIP3-mediated mitophagy in m.3635G>A related LHON. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2023-J-096). RESULTS: Compared with the control group, the protein expression levels of autophagy-related markers LC3 (LC3-II/LC3-I) and LAMP1 were significantly reduced in the variant group (P < 0.05). Additionally, the protein levels of macroautophagy-related proteins ATG12, ATG7, and ATG5 were also significantly decreased (P < 0.05). Compared with the control cells, the mRNA and protein expression levels of mitophagy-associated protein BNIP3 were significantly reduced in the cells of the variant group (P < 0.05). Compared with the control group, both mRNA and protein expression levels of the mitophagy-related protein BNIP3 were significantly reduced in the variant group (P < 0.05). CONCLUSION The m.3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.
Humans ; Proto-Oncogene Proteins/metabolism* ; Mitophagy/genetics* ; Membrane Proteins/metabolism* ; Optic Atrophy, Hereditary, Leber/metabolism* ; Mitochondria/metabolism* ; Cell Line ; Male

Objective:To investigate associations of plasma D-dimer and fasting blood glucose with the outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the Department of Neurology, Dagang Hospital, Binhai New Area, Tianjin from January 2018 to December 2023 were included retrospectively. The demographic characteristics, baseline clinical data, and laboratory findings were collected. According to the modified Rankin Scale score at 3 months after onset, the patients were divided into a good outcome group (0-2) and a poor outcome group (>2). Multivariate logistic regression analysis was used to determine the independent related factors for the outcome in patients with AIS. Results:A total of 1 967 patients were enrolled, including 1 287 males(65.4%), aged 67.80±11.58 years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-7). One thousand five hundred and twenty-three patients (77.4%) had good outcome, and 444 (22.6%) had poor outcome. Univariate analysis showed that age, baseline systolic blood pressure, baseline NIHSS score, fasting blood glucose and D-dimer, as well as the proportion of patients with a history of ischemic heart disease, previous stroke or transient ischemic attack in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that older age (odds ratio [ OR] 1.286, 95% confidence interval [ CI] 1.137-1.458; P=0.037), complicated with ischemic heart disease ( OR 1.598, 95% CI 1.024-2.227; P=0.046), higher baseline systolic blood pressure ( OR 1.011, 95% CI 1.002-1.045; P=0.037), higher baseline NIHSS score ( OR 1.432, 95% CI 1.132-1.587; P<0.001), higher baseline D-dimer ( OR 4.001, 95% CI 1.839-8.703; P=0.040), and higher fasting blood glucose ( OR 1.175, 95% CI 1.078-1.282; P=0.045) were independently associated with the poor outcome. Conclusion:Higher D-dimer and fasting blood glucose are associated with the poor outcome in patients with AIS.

Objective:To explore the mechanism of BNIP3-mediated mitophagy in m. 3635G>A related Leber′s hereditary optic neuropathy (LHON).Methods:A transmitochondrial cybrid cell line derived from a Chinese LHON patient carrying the m. 3635G>A, diagnosed at the Eye Hospital of Wenzhou Medical University in September 2013, was selected as the study subject. A transmitochondrial cybrid cell line from a healthy control with an identical mitochondrial background was included as a control. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and Western blotting were employed to assess the expression of autophagy-related proteins, aiming to explore the role of BNIP3-mediated mitophagy in m. 3635G>A related LHON. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2023-J-096).Results:① Compared with the control group, the protein expression levels of autophagy-related markers LC3 (LC3-Ⅱ/LC3-Ⅰ) and LAMP1 were significantly reduced in the variant group ( P<0.05). Additionally, the protein levels of macroautophagy-related proteins ATG12, ATG7, and ATG5 were also significantly decreased ( P<0.05). ② Compared with the control cells, the mRNA and protein expression levels of mitophagy-associated protein BNIP3 were significantly reduced in the cells of the variant group ( P<0.05). Compared with the control group, both mRNA and protein expression levels of the mitophagy-related protein BNIP3 were significantly reduced in the variant group ( P<0.05). Conclusion:The m. 3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.

ObjectiveTo evaluate the methodological quality and reporting quality of published guidelines/consensuses on traditional Chinese medicine （TCM）/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for formulating guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD in the future. MethodsDatabases including PubMed， Embase， Web of Science， CNKI， Wanfang Data， and CBM and the websites of China Association of Chinese Medicine and China Association of Integrative Medicine were searched for related articles published up to September 1， 2024. Two clinical researchers independently assessed the methodological quality and reporting quality of the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD by using Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ） and Reporting Items for Practice Guidelines in Healthcare （RIGHT）. ResultsA total of nine guidelines/consensuses were included after literature screening， with four guidelines and five expert consensuses. The scores of different domains assessed by AGREE Ⅱ for the nine guidelines/consensuses were as follows： scope and purpose （47.1%）， stakeholder involvement （41.0%）， rigor of development （21.6%）， clarity of presentation （40.2%）， applicability （19.0%）， and editorial independence （19.6%）. The recommendation level of the articles was B level （recommended after revision） for four articles and C level （not recommended） for five articles. The RIGHT assessment showed high reporting rates for “Basic Information” and “Background”， while other areas needed to be improved. Currently， there was no international standard for the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and the quality of these guidelines/consensuses needed to be enhanced to ensure comprehensiveness and credibility. ConclusionThere is still potential for improving the quality of guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and AGREE Ⅱ and RIGHT checklists should be strictly followed to ensure the fairness， scientific rigor， and transparency of these guidelines/consensuses.

Objective To evaluate the efficacy and safety of Jiawei Dihuang Decoction in the treatment of vascular dementia(VD);To explore its mechanism and the VD susceptibility genesby using whole exome sequencing.Methods A total of 75 patients with VD who were hospitalized or received outpatient treatment at The Second Affiliated Hospital of Shaanxi University of Chinese Medicine were included.They were divided into the control group(37 cases,treated with conventional Western medicine)and the experimental group(38 cases,treated with conventional Western medicine+Jiawei Dihuang Decoction)using random number table method.The treatment course was 3 months.The general data,TCM syndrome scores,MMSE scores,ADL scores,Blessed scores and adverse reactions of the two groups were compared.Peripheral blood samples from 36 patients with kidney-yin deficiency type VD were selected for whole exome sequencing.Susceptible genes were screened,and the targets of Jiawei Dihuang Decoction were analyzed by network pharmacology.A"drug-gene"network was constructed,and key pathways were enriched.Results There was no statistical significance in the baseline data between the two groups(P>0.05),and they were comparable.Compared with before treatment,the MMSE scores of patients in both groups significantly increased after treatment,while TCM syndrome scores and ADL scores significantly decreased(P<0.05).Compared with the control group,the TCM syndrome scores,MMSE scores,ADL scores and clinical efficacy of the experimental group were significantly better than those of the control group(P<0.05).Moreover,the Blessed score showed that the experimental group had more advantages in improving the patients'living ability and daily habits(P<0.05).No adverse reactions were observed in both groups during the treatment period.A total of 1 250 744 single nucleotide polymorphism(SNP)loci and 37 314 insertion and deletion(InDel)loci were detected by whole exome sequencing.After screening,3 041 VD susceptibility genes were obtained.It was found that they were involved in biological processes such as the response to nutrient levels,positive regulation of the MAPK cascade,vascular processes in the circulatory system,the response to nutrients,etc.And enriched in PI3K-Akt,cholinergic/glutamatergic synapses,lipid metabolism and atherosclerosis pathways.The potential targets of 854 of Jiawei Dihuang Decoction were intersected with the susceptibility genes to obtain 353 common targets.The top 10 key genes were analyzed and found to be involved in positive regulation of cytosine-serine phosphorylation,miRNA-mediated gene silencing regulation,and the response of cells to decreased oxygen levels,etc.They were enriched in PI3K-Akt,lipid and atherosclerosis signaling pathways.Conclusion Jiawei Dihuang Decoction can alleviate the symptoms of patients with VD,protect cognitive function,enhance their ability of daily living,and has good safety profile.Its mechanism may involve regulating susceptibility genes through PI3K-Akt signaling pathway and lipid atherosclerosis signaling pathway,and improving lipid metabolism,inflammatory response and oxidative stress.